| 1. |
|
|
| 2. |
- Aad, G, et al.
(author)
-
- 2015
-
swepub:Mat__t
|
|
| 3. |
- Ruilope, LM, et al.
(author)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Lestinsky, M., et al.
(author)
-
Physics book: CRYRING@ESR
- 2016
-
In: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
-
Research review (peer-reviewed)abstract
- The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
|
|
| 9. |
- Akerman, Ildem, et al.
(author)
-
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
- 2017
-
In: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 25:2, s. 400-411
-
Journal article (peer-reviewed)abstract
- Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
|
|
| 10. |
- Cao, Dafu, et al.
(author)
-
Study on the flexural behaviors of rc beams after Freeze-Thaw cycles
- 2015
-
In: International Journal of Civil Engineering. - 1735-0522. ; 13:1, s. 92-101
-
Journal article (peer-reviewed)abstract
- order to investigate the flexural behaviors of RC beams after freeze-thaw cycles, compressive strength test of concrete cubes after 0, 50, 100, 125 freeze-thaw cycles were made, and static flexural experiment of 48 RC beams after 0, 50, 100, 125 freeze-thaw cycles were made. The relationships of relative compressive strength, mass loss rate, relative dynamic elastic modulus and numbers of freeze-thaw cycles were analyzed. The influences of different numbers of freeze-thaw cycles on the flexural behaviors of RC beams with different concrete grades were studied. The results show that concrete cubes’ mass, relative dynamic elastic modulus and compressive strength decrease with the increasing of freeze-thaw cycles, and high-strength grade concrete could slow down the damage caused by freeze-thaw cycles. Experimental values of test beams stiffness under short-term load were smaller than theory value. Some under-reinforced RC beams occurs over-reinforced failure mode after freeze-thaw cycles. Boundary reinforcement ratio of RC beams after certain numbers of freeze-thaw cycles was derived and its correctness was verified by experiment. Current code for design of concrete structures about crack load and ultimate load are still suitable for RC beams after freeze-thaw cycles
|
|
| 11. |
- Cheng, J., et al.
(author)
-
Molecular switches of the κ opioid receptor triggered by 6′-GNTI and 5′-GNTI
- 2016
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- The κ opioid receptor (κOR) is a member of G-protein-coupled receptors, and is considered as a promising drug target for treating neurological diseases. κOR selective 6′-GNTI was proved to be a G-protein biased agonist, whereas 5′-GNTI acts as an antagonist. To investigate the molecular mechanism of how these two ligands induce different behaviors of the receptor, we built two systems containing the 5′-GNTI-κOR complex and the 6′-GNTI-κOR complex, respectively, and performed molecular dynamics simulations of the two systems. We observe that transmembrane (TM) helix 6 of the κOR rotates about 4.6° on average in the κOR-6′-GNTI complex. Detailed analyses of the simulation results indicate that E2976.58 and I2946.55 play crucial roles in the rotation of TM6. In the simulation of the κOR-5′-GNTI system, it is revealed that 5′-GNTI can stabilize TM6 in the inactive state form. In addition, the kink of TM7 is stabilized by a hydrogen bond between S3247.47 and the residue V691.42 on TM1.
|
|
| 12. |
- Dobrovolsky, Alexander, et al.
(author)
-
Fabry-Perot Microcavity Modes in Single GaP/GaNP Core/Shell Nanowires
- 2015
-
In: Small. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 1613-6810 .- 1613-6829. ; 11:47, s. 6331-6337
-
Journal article (peer-reviewed)abstract
- Semiconductor nanowires (NWs) are attracting increasing interest as nanobuilding blocks for optoelectronics and photonics. A novel material system that is highly suitable for these applications are GaNP NWs. In this article, we show that individual GaP/GaNP core/shell nanowires (NWs) grown by molecular beam epitaxy on Si substrates can act as Fabry-Perot (FP) microcavities. This conclusion is based on results of microphotoluminescence (μ-PL) measurements performed on individual NWs, which reveal periodic undulations of the PL intensity that follow an expected pattern of FP cavity modes. The cavity is concluded to be formed along the NW axis with the end facets acting as reflecting mirrors. The formation of the FP modes is shown to be facilitated by an increasing index contrast with the surrounding media. Spectral dependence of the group refractive index is also determined for the studied NWs. The observation of the FP microcavity modes in the GaP/GaNP core/shell NWs can be considered as a first step toward achieving lasing in this quasidirect bandgap semiconductor in the NW geometry.
|
|
| 13. |
- Duan, Y., et al.
(author)
-
Dynamics of fungal diversity and interactions with environmental elements in response to wheat straw biochar amended poultry manure composting
- 2019
-
In: Bioresource Technology. - : Elsevier Ltd. - 0960-8524 .- 1873-2976. ; , s. 410-417
-
Journal article (peer-reviewed)abstract
- The fungal dynamics and its correlation with physicochemical and gaseous emission were investigated using metagenomics and Heat map illustrator (HEMI). Five different concentrations of wheat straw biochar (WSB) were applied to poultry manure (PM) and composted for 50 days; those without the WSB treatment were used as a control. The results revealed the dominant phyla to be Chytridiomycota, Mucoromycota, Ascomycota and Basidiomycota, while Batrachochytrium, Rhizophagus, Mucor, and Puccinia were the superior genera. In particular, the diversity of Chytridiomycota and Ascomycota was more abundant among all of the treatments. Overall, the diversity of the fungal species was correspondent, but relative abundance varied significantly among all of the composts. Principle Coordinate Analysis (PCoA) and Non-Metric Multi- Dimensional Scaling (NMDS) indicated that different concentrations of WSB applied treatments have significantly distinct fungal communities. In addition, correlation analyses of fungal interactions with environmental elements via HEMI also indicate a clear difference among the treatments. Ultimately, the relative abundance of fungal composition significantly influenced the PM compost treated by the WSB.
|
|
| 14. |
- Hussain, M., et al.
(author)
-
ATAD2 in cancer : a pharmacologically challenging but tractable target
- 2018
-
In: Expert opinion on therapeutic targets. - : Taylor and Francis Ltd. - 1472-8222 .- 1744-7631. ; 22:1, s. 85-96
-
Journal article (peer-reviewed)abstract
- Introduction: ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2’s bromodomain (BRD) may be a very challenging task. ATAD2’s BRD has been predicted as a ‘difficult to drug’ or ‘least druggable’ target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding. Areas covered: In this review, after shedding light on the multifaceted roles of ATAD2 in normal physiology as well as in cancer-etiology, we discuss technical challenges rendered by ATAD2’s BRD active site and the recent drug discovery efforts to find small molecule inhibitors against it. Expert opinion: The identification of a novel low-nanomolar semi-permeable chemical probe against ATAD2’s BRD by recent drug discovery campaign has demonstrated it to be a pharmacologically tractable target. Nevertheless, the development of high quality bioavailable inhibitors against ATAD2 is still a pending task. Moreover, ATAD2 may also potentially be utilized as a promising target for future development of RNAi-based therapy to treat cancers.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Shi, C., et al.
(author)
-
Molecular dynamics simulations indicate that DNA bases using graphene nanopores can be identified by their translocation times
- 2015
-
In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:13, s. 9389-9395
-
Journal article (peer-reviewed)abstract
- The improvement of the resolution of DNA sequencing by nanopore technology is very important for its real-life application. In this paper, we report our work on using molecular dynamics simulation to study the dependence of DNA sequencing on the translocation time of DNA through a graphene nanopore, using the single-strand DNA fragment translocation through graphene nanopores with diameters down to ∼2 nm as examples. We found that A, T, C, and G could be identified by the difference in the translocation time between different types of nucleotides through 2 nm graphene nanopores. In particular, the recognition of the graphene nanopore for different nucleotides can be greatly enhanced in a low electric field. Our study suggests that the recognition of a graphene nanopore by different nucleotides is the key factor for sequencing DNA by translocation time. Our study also indicates that the surface of a graphene nanopore can be modified to increase the recognition of nucleotides and to improve the resolution of DNA sequencing based on the DNA translocation time with a suitable electric field.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Wang, Z., et al.
(author)
-
Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton
- 2017
-
In: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 139:44, s. 15784-15791
-
Journal article (peer-reviewed)abstract
- DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.
|
|
| 22. |
- Ye, Y, et al.
(author)
-
The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study
- 2015
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 11685-
-
Journal article (peer-reviewed)abstract
- The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency and in conditions in which bone marrow myelopoiesis is negatively affected.
|
|
| 23. |
- Yuan, S., et al.
(author)
-
High-gain broadband organolead trihalide perovskite photodetector based on a bipolar heterojunction phototransistor
- 2018
-
In: Organic electronics. - : Elsevier. - 1566-1199 .- 1878-5530. ; 57, s. 7-13
-
Journal article (peer-reviewed)abstract
- Both a favorable material and designed structure are essential for a high-performance photodetector. For the excellent physical properties of organolead trihalide perovskites, with CH3NH3PbI3 films serving as a base layer, a bipolar heterojunction phototransistor-type perovskite photodetector is proposed. Benefiting from this bipolar heterojunction structure, which is characterized by high gain and low work voltage, an optimized device exhibits high performance with a photoresponsivity of 125 AW−1 and an external efficiency of 3.62 × 104% at 427 nm with a low work voltage of 0.7 V. Additionally, such phototransistors have a broad photoresponsivity from 360 to 820 nm. These results demonstrate that the bipolar heterojunction phototransistor, which is widely used in inorganic materials, is a promising structure for organolead trihalide perovskite optoelectronic devices, paving a new way for developing high-performance photodetectors.
|
|
